Focal adhesion kinase as an immunotherapeutic target.
BACKGROUND
Focal adhesion kinase (FAK) is a ubiquitously expressed non-receptor tyrosine kinase involved in cancer progression and metastasis that is found overexpressed in a large number of tumors such as breast, colon, prostate, melanoma, head and neck, lung and ovary. Thus, FAK could be an attractive tumor associated antigen (TAA) for developing immunotherapy against a broad type of malignancies. In this study, we determined whether predicted T cell epitopes from FAK would be able to induce anti-tumor immune cellular responses.


METHODS
To validate FAK as a TAA recognized by CD4 helper T lymphocytes (HTL), we have combined the use of predictive peptide/MHC class II binding algorithms with in vitro vaccination of CD4 T lymphocytes from healthy individuals and melanoma patients.


RESULTS
Two synthetic peptides, FAK(143-157) and FAK(1,000-1,014), induced HTL responses that directly recognized FAK-expressing tumor cells and autologous dendritic cells pulsed with FAK-expressing tumor cell lysates in an HLA class II-restricted manner. Moreover, since the FAK peptides were recognized by melanoma patient's CD4 T cells, this is indicative that T cell precursors reactive with FAK already exist in peripheral blood of these patients.


CONCLUSIONS
Our results provide evidence that FAK functions as a TAA and describe peptide epitopes that may be used for designing T cell-based immunotherapy for FAK-expressing cancers, which could be used in combination with newly developed FAK inhibitors.
Kobayashi
Hiroya
H
Department of Pathology, Asahikawa Medical College, Asahikawa, Japan.
Azumi
Makoto
M
Kimura
Yuka
Y
Sato
Keisuke
K
Aoki
Naoko
N
Kimura
Shoji
S
Honma
Masaru
M
Iizuka
Hajime
H
Tateno
Masatoshi
M
Celis
Esteban
E
D000951:Antigens, Neoplasm / Q000276:immunology; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000276:immunology*; D005802:Genes, MHC Class II / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D007167:Immunotherapy; D008545:Melanoma / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D051416:Focal Adhesion Protein-Tyrosine Kinases